Application of antibody-drug conjugates in locally advanced or metastatic urothelial carcinoma: mechanisms, treatment-related adverse events, and management strategies

Locally advanced or metastatic urothelial carcinoma (la/mUC) is a highly aggressive malignancy with a poor prognosis. For decades, platinum-based chemotherapy has remained the cornerstone of first-line treatment. In recent years, antibody-drug conjugates (ADCs), leveraging their ability to precisely target tumor sites, have emerged as important therapeutic options, advancing into second-line and even first-line settings. The advent of ADCs has not only provided new alternatives for patients ineligible for chemotherapy but also offered a variety of treatment regimens. These agents enhance therapeutic efficacy while being adaptable to different patient subtypes, achieving satisfactory outcomes with relatively manageable safety profiles. Consequently, ADCs have rapidly become a clinical star and a research hotspot. Enfortumab Vedotin (EV), Sacituzumab Govitecan (SG), and Disitamab Vedotin (DV) are currently among the most studied ADCs in la/mUC. However, as the clinical experience with ADCs is still relatively nascent, accumulating knowledge regarding their safety is ongoing. It is crucial for clinicians to understand the mechanisms of action of ADCs and to master the management, including prevention and mitigation strategies, of treatment-related adverse events (TRAEs) associated with different ADC agents.